title: Design of a novel bilayered gastric mucoadhesive system for localized and unidirectional release of lamotrigine.
abstract: Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P. A 2(3) full factorial design was constructed for this study and the tablets were optimized for parameters like tablet size, shape, ex vivo mucoadhesive properties and unidirectional drug release. Oval tablets with an average size of 14 mm diameter were set optimum. Maximum mucoadhesive bond strength of 79.3 ± 0.91 * 10(3) dyn/cm(2) was achieved with carbopol when used in combination with a synergistic resin polymer. All the tested formulations presented a mucoadhesion time of greater than 12 h. The incorporation of methacrylic polymers in the lower layer ensured unidirectional drug release from the bilayered tablets. The unidirectional drug release was confirmed after comparing the dissolution results of paddle method with those of a modified basket method. Model independent similarity and dissimilarity factor methods were used for the comparison of dissolution results. Controlled drug release profiles with zero order kinetics were obtained with polyox and HPMC K15M which reported t 90% at 6th and 12th hours, respectively. The "n" value with polyox was 0.992 and that with HPMC K15M was 0.946 indicating an approximate case II transport. These two formulations showed the potential for oral administration of lamotrigine as bilayered gastric mucoadhesive tablets by yielding highest similarity factor values, 96.06 and 92.47, respectively, between the paddle and modified basket method dissolution release profiles apart from reporting the best tablet physical properties and maximum mucoadhesive strength.
authors.affiliation: Department of Pharmaceutics, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad 500 028, Andhra Pradesh, India ; Research and Development Centre, RA Chem Pharma Limited, Road No. 18, IDA, Nacharam, Hyderabad 500 076, Andhra Pradesh, India.
authors.forename: K
authors.initials: K
authors.lastname: Mohana Raghava Srivalli
authors.forename: P K
authors.initials: PK
authors.lastname: Lakshmi
authors.forename: J
authors.initials: J
authors.lastname: Balasubramaniam
keywords: #, sieve number; %, percentage; 23 full factorial design; API, active pharmaceutical ingredient; BCS, biopharmaceutical classification system; BGMT, bilayered gastric mucoadhesive tablets; Bilayered gastric mucoadhesive tablets; CR layer, control release layer; G, grams; HCl, hydrochloric acid; Lamotrigine; MA layer, mucoadhesive layer; MDT, mean dissolution time; Methacrylic polymers; Mg, milligrams; Modified basket dissolution model; USP, United States pharmacopoeia; UV, ultra violet; Unidirectional drug release; Zero order release; cms, centimetres; f1, difference factor; f2, similarity factor; h, hours; mL, millilitre; min, minute; mm, millimetre; n, release exponent (power law Korsmeyer Peppas equation); nm, nanometre; r2, correlation coefficient; rpm, revolution per minute; sec, seconds; °C, degrees centigrade; ≈, approximately equivalent to